We have investigated hairy cell leukemia cells using monoclonal antibodies developed in our laboratory. These antibodies have varying degrees of specificity for hairy cells. In an effort to define the unknown normal cell equivalent of the leukemic hairy cell, a new relationship of hairy cells with activated-B cells and with endothelial cells has been established. Current evidence suggests that the activated-B cell is the normal cell equivalent of the leukemic hairy cell. This has been demonstrated in several ways, including electron microscope studies using the immunogold method with the monoclonal antibodies. As a byproduct of this research, a monoclonal antibody against hairy cells has been shown to define a unique differentiation stage of human B cells and may detect an important receptor molecule on B cells. The functional role of the antigens defined by two monoclonal antibodies is under intensive investigation. (MI)